There is a growing need for organ transplantation in HIV-infected (HIV+) individuals due to a rising prevalence of end-stage renal disease and end-stage liver disease. Studies demonstrate excellent outcomes of transplantation in HIV+ individuals using HIV-uninfected (HIV-) donors. However, there is a profound organ shortage, with extremely long waiting times, and a higher waitlist mortality for HIV+ individuals in particular. A novel source of organs specific to HIV+ individuals is desperately needed. Organs from HIVDD are a unique potential resource for HIV+ individuals on the transplant waitlist. By expanding the donor pool, the use of HIVDD could also decrease the wait time for HIV- individuals, resulting in a far-reaching public health impact. Recognition of this need led our group to write the HIV Organ Policy Equity (HOPE) Act which passed Congress and was recently signed by President Obama on November 21, 2013, calling for research on HIV-to-HIV organ transplants. The HOPE Act directs the Secretary of HHS to develop and publish guidelines for the conduct of research and safety relating to HIVDD organ transplantation, and further empowers the Secretary to determine at what point to allow open transplantation of HIVDD organs. In South Africa, Dr. Elmi Muller has pioneered the use of organs from HIVDD for HIV+ renal transplant candidates and seen excellent outcomes. However there are key differences between the US and S Africa that will impact safety, organ quality and outcomes of HIV-to-HIV transplantation: prevalence and causes of organ disease, access to transplantation, waitlist mortality, HIV prevalence, number of HIV deaths/year and HIVDD race, age, cause of death, co-morbidities, HIV viral load, CD4 T cell count, access to antiretroviral therapy (ART) and ART resistance. To evaluate the safety, feasibility and effectiveness of HIV-to-HIV transplantation in the US, we propose to design and plan a multicenter prospective study: HOPE in Action. We have the support of more than 20 major US transplant centers across the US who are committed to assisting us in the design and implementation of the study which will look at kidney and liver transplant using organs from HIVDD. The primary outcomes will be patient survival and graft survival, compared to 1) outcomes of HIV+ transplantation using HIV- donors and 2) waiting for the next available HIV- organ (survival benefit). Secondary outcomes will include incidence of graft rejection, recurrence of HIV-AN, incidence of HIV- superinfection, changes in HIV levels and CD4 T-cells, ART resistance, and incidence of infections. Our group has long-standing experience in NIH-funded multicenter studies. We have established critical infrastructure with the Organ Procurement Transplant Network and we have recruited Dr. Peter Stock, the PI of the NIH- funded HIV Multisite Study and Dr. Elmi Muller, the world's expert on transplantation using HIV+ donors to serve as consultants. This R34 grant will enable timely initiation of the proposed clinical trial, which will provide critical information on the safety, feasibility and effectiveness of HIV-to-HIV transplantation.